COAPT Trial of Transcatheter Mitral Valve Repair in Patients with Heart Failure

COAPT Trial of Transcatheter Mitral Valve Repair in Patients with Heart Failure

Patients with heart failure and left ventricular dilatation may have secondary or functional mitral regurgitation. This is due to alteration of the left ventricular geometry producing changes in the functioning of papillary muscles and chordae tendineae and poor coaptation of the mitral leaflets. Secondary mitral regurgitation causes volume overloading of the left ventricle and is associated with reduced survival, increased hospitalization rates and decreased quality of life [1, 2]. Secondary mitral regurgitation can be reduced by guideline directed medical therapy and cardiac resynchronization therapy. This will also provide symptomatic relief and improve left ventricular function.

EVEREST II trial comparing percutaneous mitral valve repair and surgery for mitral regurgitation had concluded that percutaneous repair was less effective at reducing mitral regurgitation than conventional surgery. But percutaneous repair was associated with superior safety and similar improvements in clinical outcome. An exploratory subgroup analysis of EVEREST II trial showed that surgery was not superior to percutaneous treatment in functional mitral regurgitation [3]. This observation was the reason for initiating the COAPT Trial of Transcatheter Mitral Valve Repair in Patients with Heart Failure [4].

COAPT trial was conducted at 78 sites across United States and Canada and enrolled patients with heart failure having moderate to severe or severe secondary mitral regurgitation who were symptomatic despite maximal tolerated doses of guideline directed medical therapy. They were randomly assigned to either transcatheter mitral valve repair plus GDMT or GDMT alone. Primary effectiveness end point was hospitalization for heart failure within 2 years of follow up. Primary safety endpoint was freedom from device related complications at one year.

Freedom from device related complications at one year was 96.6%. Annualized rate of hospitalization for heart failure within 2 years was 35.8% per patient year in the device group and 67.9% per patient year in the control group. All cause mortality was 29.1% in the device group and 46.1% in the control group. Similar benefit was noted in those who had ischemic and nonischemic cardiomyopathy. Same was true of those at high risk for surgery vs those not at high risk of surgery. Benefits were found to be independent of the grade of mitral regurgitation, left ventricular volume and function at baseline. Device treated patients also had better quality of life and functional capacity at 2 years compared to those on GDMT alone [4].

Improvements were attributed to the decrease in severity of secondary mitral regurgitation by transcatheter mitral leaflet approximation by the device. Decrease in hospitalization for heart failure was noted within a month of device therapy while mortality benefits occured more than a year after treatment. Procedural success was noted in 98% of cases with a decrease in mitral regurgitation grade of 2+ in 95%. A potential bias in the study was that the device would be visible on imaging at follow up so that it would make the assessment not a truly blinded one. But that would not affect the hospitalization rate and mortality rate which showed improvement in the trial.

References

1. Sannino A, Smith RL 2nd, Schiattarella GG, Trimarco B, Esposito G, Grayburn PA. Survival and Cardiovascular Outcomes of Patients With Secondary Mitral Regurgitation: A Systematic Review and Meta-analysis. JAMA Cardiol. 2017 Oct 1;2(10):1130-1139. doi: 10.1001/jamacardio.2017.2976. PMID: 28877291; PMCID: PMC5710448.
2. Goliasch G, Bartko PE, Pavo N, Neuhold S, Wurm R, Mascherbauer J, Lang IM, Strunk G, Hülsmann M. Refining the prognostic impact of functional mitral regurgitation in chronic heart failure. Eur Heart J. 2018 Jan 1;39(1):39-46. doi: 10.1093/eurheartj/ehx402. PMID: 29020337.
3. Feldman T, Foster E, Glower DD, Kar S, Rinaldi MJ, Fail PS, Smalling RW, Siegel R, Rose GA, Engeron E, Loghin C, Trento A, Skipper ER, Fudge T, Letsou GV, Massaro JM, Mauri L; EVEREST II Investigators. Percutaneous repair or surgery for mitral regurgitation. N Engl J Med. 2011 Apr 14;364(15):1395-406. doi: 10.1056/NEJMoa1009355. Epub 2011 Apr 4. Erratum in: N Engl J Med. 2011 Jul 14;365(2):189. Glower, Donald G [corrected to Glower, Donald D]. PMID: 21463154.
4. Stone GW, Lindenfeld J, Abraham WT, Kar S, Lim DS, Mishell JM, Whisenant B, Grayburn PA, Rinaldi M, Kapadia SR, Rajagopal V, Sarembock IJ, Brieke A, Marx SO, Cohen DJ, Weissman NJ, Mack MJ; COAPT Investigators. Transcatheter Mitral-Valve Repair in Patients with Heart Failure. N Engl J Med. 2018 Dec 13;379(24):2307-2318. doi: 10.1056/NEJMoa1806640. Epub 2018 Sep 23. PMID: 30280640.